Temporomandibular disorders (TMD), characterized by persistent pain in the cheek and jaw area of the face, affect approximately 1 in 10 women at some point in their lives. TMD treatments primarily focus on peripheral factors; however, many patients with TMD show no signs of peripheral damage. It is now known that many chronic pain conditions, including TMD, involve pain centralization, meaning the pain is generated and maintained by central, rather than peripheral, nervous system processes. There are currently no well accepted means through which centralized TMD pain can be identified in the clinic, and the failure to properly identify these centralized cases means that ineffective peripheral treatments are administered. The specific aims of this project are to 1) Demonstrate that structural, functional, and neurochemical abnormalities exist in TMD that are similar to those reported in other centralized pain conditions, 2) Utilize questionnaire and quantitative sensory testing measures that can accurately detect centralized pain to place patients on a continuum from peripheral to centralized, and show that the brains of centralized, but not peripheral, patients differ significantly from healthy controls, and 3) Determine the measures of centralization and brain morphology, function, and chemistry that predict lack of improvement from a peripherally targeted treatment regimen, to show that centralized TMD patients do not respond as well to treatments that fail to target their pathology. The primary goal of the mentored (K99) portion of the award is to give the candidate the additional training in neuroimaging necessary for him to obtain a tenure track faculty position and successfully run his own independent research program. The K99 phase will take place at the University of Michigan, under the mentorship of Drs. Daniel Clauw, Richard Harris, and David Williams, who are world-renowned experts in centralized pain conditions, pain neuroimaging, and pain psychometrics, respectively. Dr. William Maixner (Duke University), a world- leading expert on TMD, will also serve as a mentor; he will advise the candidate on the clinically relevant aspects of TMD and help the candidate network with other more established TMD researchers. The University of Michigan is ideal for the K99 phase of the project because of the available resources, including faculty who are committed to clinical pain research and mentoring, research-devoted magnetic resonance imaging (MRI) scanners and state-of-the-art pain testing equipment, and ample laboratory and office space at the Chronic Pain and Fatigue Research Center. Upon completing the K99 portion of the award, the candidate will be well suited to make the transition to tenure-track faculty.